Abstract

ADVERSE EFFECTS OF SGLT2 INHIBITORS: A SYSTEMIC REVIEW

Udaya M. Kabadi*,?, Joe Herba,? and Sarah Exley,?

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Abstract

SGLT2 inhibitors are modest in efficacy lowering glycemia, while incurring undue cost burden to the patients. Moreover, the mechanism of action may be detrimental to the quality of life attributed to polyuria, nocturia and consequential dehydration resulting in orthostatic hypotension and serious adverse outcomes secondary to increased serum viscosity. Alternatively, electrolyte imbalances, including hypernatremia, hyperkalemia, hypercalcemia, hyper or hypophosphatemia and ketoacidosis with or without hyperglycemia as well as accumulation of other unmeasured anions and declining renal function evident by rising serum creatinine and urea nitrogen concentrations are likely to escalate costs and contribute further decline in quality of life and even mortality. Finally, rise in LDL cholesterol may further raise serum viscosity and both may be responsible for increased strokes and lower limb amputations. Therefore, well established greater risks of occurrence of several serious adverse outcomes, such as recurrent genitourinary infections, acute pyelonephritis and sepsis, ketoacidosis, strokes, lower limb amputations, osteoporosis and fractures, acute pancreatitis, as well as other anticipated outcomes; e.g. renal calculi, nephrocalcinosis, uric acid nephropathy due to hypercalciuria and uricosuria, are likely to further increase the costs and compromise the quality of life. Moreover, these findings may have prompted the FDA and European regulatory agency to issue far too many cautions and alerts. However, the hanging question of bladder cancer and the lack of knowledge of the effects of long term exposure of genitourinary tract to hyperglycemic hyperosmolar urine, may require long term monitoring.

Keywords: SGLT2 Inhibitors, Side effects, Complications, Safety, Efficacy.